Acute murine cytomegalovirus disrupts established transplantation tolerance and causes recipient allo-sensitization

Shuangjin Yu, Anil Dangi, Melanie Burnette, Michael M. Abecassis, Edward B. Thorp, Xunrong Luo

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


We have previously shown that acute cytomegalovirus (CMV) infection disrupts the induction of transplantation tolerance. However, what impact acute CMV infection would have on the maintenance of established tolerance and on subsequent recipient allo-sensitization is a clinically important unanswered question. Here we used an allogeneic murine islet transplantation tolerance model to examine the impact of acute CMV infection on: (a) disruption of established transplantation tolerance during tolerance maintenance; and (b) the possibility of recipient allo-sensitization by CMV-mediated disruption of stable tolerance. We demonstrated that acute CMV infection abrogated transplantation tolerance during the maintenance stage in 50%-60% recipients. We further demonstrated that acute CMV infection–mediated tolerance disruption led to recipient allo-sensitization by reverting the tolerant state of allo-specific T cells and promoting their differentiation to allo-specific memory cells. Consequently, a second same-donor islet allograft was rejected in an accelerated fashion by these recipients. Our study therefore supports close monitoring for allo-sensitization in previously tolerant transplant recipients in whom tolerance maintenance is disrupted by an episode of acute CMV infection.

Original languageEnglish (US)
Pages (from-to)515-524
Number of pages10
JournalAmerican Journal of Transplantation
Issue number2
StatePublished - Feb 2021


  • alloantibody
  • basic (laboratory) research/science
  • immunobiology
  • immunosuppression/immune modulation
  • infection and infectious agents - viral: Cytomegalovirus (CMV)
  • islet transplantation
  • re-transplantation
  • rejection: T cell–mediated (TCMR)
  • tolerance

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)


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